Is CD55 p.Ala227Pro (c.679G>C) pathogenic?

CD55 p.Ala227Pro (c.679G>C) is classified Benign/Likely benign in CD55 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0799); Low-frequency (popmax 1.83%, afr).

How common is CD55 p.Ala227Pro (c.679G>C) in the general population?

CD55 p.Ala227Pro (c.679G>C) is low-frequency (popmax 1.83%, afr) (gnomAD).

What do computational predictors say about CD55 p.Ala227Pro (c.679G>C)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

CD55 p.Ala227Pro

c.679G>C · rs60822373 · VCV1164353

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.83%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -4.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP -1
Regional constraint	o/e 0.90	unconstrained · MANE · 33 kb · p 0.17 · regional, not allelic
Overall
CADD	17.07	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.83% African / African-American · 1,374/74,898 alleles

Filtering AF 1.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.72%

Overall 0.108% 1,748/1,611,430 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.83%	55
Middle Eastern	0.496%	202
Admixed American	0.209%	478
Ashkenazi Jewishnot grpmax-eligible	0.176%	568
Remaining individualsnot grpmax-eligible	0.16%	624
European (non-Finnish)	0.00535%	18,707
South Asian	0.00442%	22,635

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CD55
Protein: p.Ala227Pro
Coding: c.679G>C
MANE Select: NM_000574
dbSNP: rs60822373
Type: single nucleotide variant
Location: chr1:207331122 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 227: a disulfide bond; a UniProt-annotated variant site (in cr(a-) antigen); the sushi 4 domain; an α-helix

Full CD55 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD55 c.286+1G>A Likely pathogenic ★★ same type
CD55 c.286+2T>G Likely pathogenic ★★ same type
CD55 p.Glu50Ter Pathogenic/Likely pathogenic ★★ same type
CD55 p.Trp213Ter Pathogenic/Likely pathogenic ★★ same type
CD55 c.1081+1G>C Uncertain significance ★★ same type
CD55 p.Arg221Ser Uncertain significance ★★ ⚠ same type
CD55 p.Arg357Cys Uncertain significance ★★ ⚠ same type
CD55 p.Arg357His Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cd55-p-ala227pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown